A Phase 3 Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid

Bullous Pemphigoid Clinical Trial

— BALLAD+  

Official title:

An Open-label Extension Study of ARGX-113-2009 to Evaluate the Long Term Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05681481
• Other study ID #: ARGX-113-2010
• Status: Recruiting
• Phase: Phase 3
• Start date: March 22, 2023
• Est. completion date: March 6, 2026

Study information

• Verified date: April 2024
• Source: argenx
• Contact: Sabine Coppieters, MD
• Phone: 857-350-4834
• Email: clinicaltrials[@]argenx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ARGX-113-2010 is an open-label extension study with the aim to provide supporting evidence that efgartigimod PH20 SC is a safe and effective long-term treatment for bullous pemphigoid (BP), providing symptom control and eventually remission, while also reducing the cumulative exposure to oral corticosteroids (OCS). All participants who complete the end-of-treatment period (EoTP) visit at week 36 in ARGX-113-2009 will be invited to enroll. In ARGX-113-2009, participants received efgartigimod PH20 SC or placebo with concurrent OCS, or rescue therapy (without efgartigimod PH20 SC or placebo). Depending on their clinical status at the time of rollover into ARGX-113-2010, participants may stop, continue or initiate efgartigimod PH20 SC treatment. In ARGX-113-2010, participants will stop efgartigimod PH20 SC treatment when they achieve complete remission (CR) or partial remission (PR) while being off other concurrent BP therapy for at least 8 weeks. Participants not in CR or PR while off OCS for ≥8 weeks and not on rescue therapy will either start or continue efgartigimod PH20 SC treatment, while maintaining the treatment allocation of ARGX-113-2009 blinded. Participants may also be retreated with efgartigimod PH20 SC after a relapse. In this study, loading doses of 2000 mg (on day 1 and day 8 of a treatment course) and weekly maintenance doses of 1000 mg will be used.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 6, 2026
• Est. primary completion date: January 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has completed the week 36 visit of ARGX-113-2009
• Is capable of providing signed informed consent and complying with protocol requirements
• Agrees to use contraceptive measures consistent with local regulations and the following: Women of childbearing potential must have a negative urine pregnancy test at baseline before receiving IMP and must use one of the contraception methods described in the protocol from signing the ICF until the last dose of IMP

Exclusion Criteria:

• Clinically significant disease, recent major surgery (within 3 months of baseline), or intends to have surgery during the study; or any other medical condition that, in the investigator's opinion would confound the results of the study or put the participant at undue risk
• Known hypersensitivity to IMP or 1 of its excipients
• Permanently discontinued IMP in ARGX-113-2009 due to an AE considered related to IMP and for whom the benefit/risk balance is not considered positive

Related Conditions & MeSH terms

• Bullous Pemphigoid
• Pemphigoid, Bullous

Intervention

Biological:
• efgartigimod PH20 SC
Subcutaneous injection of efgartigimod coformulated with rHuPH20, a permeation enhancer

Drug:
• Prednisone
Oral Prednisone

Locations

Country	Name	City	State
Australia	Premier Specialists	Kogarah
Bulgaria	Diagnostic and Consulting Center Aleksandrovska EOOD	Sofia
China	West China Hospital of Sichuan University	Chengdu
Croatia	Poliklinika Solmed	Zagreb
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Universitatsklinikum Dusseldorf	Düsseldorf
Germany	Universitatsklinikum Schleswig-Holstein	Kiel
Germany	LMU Klinikum der Universität	München
Greece	Hospital of Venereal and Skin Diseases A.Syggros	Athens
Greece	Hospital of Venereal and Skin Diseases A.Syggros	Athens
Hungary	Semmelweis Egyetem	Budapest
Israel	Sheba Medical Center - PPDS	Ramat Gan
Italy	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele	Catania
Italy	Azienda Sanitaria Di Firenze	Firenze
Italy	Azienda USL Toscana Centro - Ospidale Piero Palagi	Firenze
Italy	Ospedale Policlinico San Martino	Genova
Italy	Fondazione IRCCS Policlinico San Matteo di Pavia	Pavia
Italy	Fondazione Policlinico Universitario A. Gemelli	Rome
Japan	Hokkaido University Hospital	Sapporo
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Serbia	University Clinical Center of Serbia - PPDS	Belgrade
Slovakia	Fakultna nemocnica Trnava	Trnava
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Doctor Peset	Valencia
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	First OC Dermatology	Fountain Valley	California
United States	Miami Dermatology and Laser Institute	Miami	Florida
United States	Saint Louis University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  China,  Croatia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	Incidence of treatment-emergent adverse events	Up to 56 weeks
Primary	Severity of treatment-emergent adverse events	Severity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events ( CTCAE) definitions (current version): Grade 1 (mild) to Grade 5 (death related to adverse event)	Up to 56 weeks
Primary	Incidence of serious adverse events	Incidence of serious adverse events	Up to 56 weeks
Primary	Severity of serious adverse events	Severity of serious adverse events	Up to 56 weeks
Primary	Incidence of adverse events of special interest	Incidence of adverse events of special interest	Up to 56 weeks
Primary	Severity of adverse events of special interest	Severity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events ( CTCAE) definitions (current version): Grade 1 (mild) to Grade 5 (death related to adverse event)	Up to 56 weeks
Primary	Rate of treatment discontinuation because of safety concerns	Rate of treatment discontinuation because of safety concerns	Up to 56 weeks
Secondary	Proportion of participants achieving complete remission while off oral corticosteroids for = 8 weeks	Proportion of participants achieving complete remission while off oral corticosteroids for = 8 weeks	Up to 56 weeks
Secondary	Proportion of participants achieving complete remission or partial remission while off oral corticosteroids for = 8 weeks	Proportion of participants achieving complete remission or partial remission while off oral corticosteroids for = 8 weeks	Up to 56 weeks
Secondary	Proportion of participants achieving complete remission while on minimal oral corticosteroids therapy for = 8 weeks	Minimal oral corticosteroid therapy is defined as =0.10 mg/kg/day of prednisone (or an equivalent dose of another oral corticosteroid)	Up to 56 weeks
Secondary	Proportion of participants achieving complete remission while off both oral corticosteroids and efgartigimod PH20 SC for = 8 weeks	Proportion of participants achieving complete remission while off both oral corticosteroids and efgartigimod PH20 SC for = 8 weeks	Up to 56 weeks
Secondary	Proportion of participants achieving complete remission or partial remission while off both oral corticosteroids and efgartigimod PH20 SC for = 8 weeks	Proportion of participants achieving complete remission or partial remission while off both oral corticosteroids and efgartigimod PH20 SC for = 8 weeks	Up to 56 weeks
Secondary	Duration of sustained remission	Duration of sustained remission	Up to 56 weeks
Secondary	Proportion of participants who relapse	Proportion of participants who relapse	Up to 56 weeks
Secondary	Time to relapse	Time to relapse	Up to 56 weeks
Secondary	Incidence of relapse	Incidence of relapse	Up to 56 weeks
Secondary	Severity of relapse	Severity of relapse will be assessed based on the Bullous Pemphigoid Disease Area Index (BPDAI)	Up to 56 weeks
Secondary	Bullous Pemphigoid Disease Area Index (BPDAI) activity scores over time	Bullous Pemphigoid Disease Area Index (BPDAI) activity scores over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 2, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Bullous Pemphigoid Disease Area Index (BPDAI) activity scores over time	Bullous Pemphigoid Disease Area Index (BPDAI) activity scores over time	For participants continuing/starting efgartigimod PH20 SC treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 4 weeks until efgartigimod stop, every 8 weeks after efgartigimod stop and at weeks 48, 52 and 56.
Secondary	Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) scores over time	Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) scores over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 2, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) scores over time	Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) scores over time	For participants continuing/starting efgartigimod PH20 SC treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 4 weeks until efgartigimod stop, every 8 weeks after efgartigimod stop and at weeks 48, 52 and 56.
Secondary	Itch Numerical Rating Scale (NRS) over time	Itch Numerical Rating Scale (NRS) over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 2, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Itch Numerical Rating Scale (NRS) over time	Itch Numerical Rating Scale (NRS) over time	For participants continuing/starting efgartigimod PH20 SC treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 4 weeks until efgartigimod stop, every 8 weeks after efgartigimod stop and at weeks 48, 52 and 56.
Secondary	Rate of treatment failure	Rate of treatment failure	Up to 56 weeks
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index - Aggregate Improvement Score (GTI-AIS) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index - Aggregate Improvement Score (GTI-AIS) over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 24 and 48.
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index - Aggregate Improvement Score (GTI-AIS) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index - Aggregate Improvement Score (GTI-AIS) over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: weeks 0, 8, every 16 weeks until and after efgartigimod treatment stop and at week 48.
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Cumulative Worsening Score (GTI-CWS) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Cumulative Worsening Score (GTI-CWS) over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 24 and 48.
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Cumulative Worsening Score (GTI-CWS) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Cumulative Worsening Score (GTI-CWS) over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: weeks 0, 8, every 16 weeks until and after efgartigimod treatment stop and at week 48.
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Specific List (GTI-SL) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Specific List (GTI-SL) over time	For participants not requiring treatment with efgartigimod at rollover: at weeks 0, 24 and 48.
Secondary	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Specific List (GTI-SL) over time	Glucocorticoid Toxicity Index (GTI)-related scores, including the Glucocorticoid Toxicity Index Specific List (GTI-SL) over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: weeks 0, 8, every 16 weeks until and after efgartigimod treatment stop and at week 48.
Secondary	EQ-5D-5L scores over time	EQ-5D-5L scores over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 24 and 48.
Secondary	EQ-5D-5L scores over time	EQ-5D-5L scores over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: at weeks 0, 8, every 16 weeks until and after efgartigimod PH20 SC treatment stop and at week 48.
Secondary	Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time	Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 24 and 48.
Secondary	Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time	Autoimmune Bullous Disease Quality of Life (ABQoL) scores over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: at weeks 0, 8, every 16 weeks until and after efgartigimod PH20 SC treatment stop and at week 48.
Secondary	Dermatology Life Quality Index (DLQI) scores over time	Dermatology Life Quality Index (DLQI) scores over time	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 24 and 48.
Secondary	Dermatology Life Quality Index (DLQI) scores over time	Dermatology Life Quality Index (DLQI) scores over time	For participants continuing/starting efgartigimod treatment at rollover or relapse: at weeks 0, 8, every 16 weeks until and after efgartigimod PH20 SC treatment stop and at week 48.
Secondary	Percent changes from baseline over time for anti-BP180 and anti-BP-230 antibody levels	Percent changes from baseline over time for anti-BP180 and anti-BP-230 antibody levels	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 2, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Percent changes from baseline over time for anti-BP180 and anti-BP-230 antibody levels	Percent changes from baseline over time for anti-BP180 and anti-BP-230 antibody levels	For participants continuing/starting efgartigimod PH20 SC treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 4 weeks to efgartigimod stop, every 8 weeks after efgartigimod stop and at weeks 48, 52 and 56.
Secondary	Incidence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	Incidence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Incidence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	Incidence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	For participants continuing/starting efgartigimod treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 8 weeks until and after efgartigimod PH20 SC stop and at weeks 48, 52 and 56.
Secondary	Prevalence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	Prevalence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	For participants not requiring treatment with efgartigimod PH20 SC at rollover: at weeks 0, 4, 8, 16, 24, 32, 40, 48 and 56.
Secondary	Prevalence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	Prevalence of antidrug antibody(ies) (ADA) against efgartigimod (serum levels)	For participants continuing/starting efgartigimod treatment at rollover or relapse: at weeks 0, 2, 4 and 8 and then every 8 weeks until and after efgartigimod PH20 SC stop and at weeks 48, 52 and 56.